| Part1:NeutrophiI-lymphocyte Ratio as a Prognostic Factor for Locally Advanced Rectal Cancer Following Neoadjuvant ChemoradiationObjective:The neutrophil-lymphocyte ratio (NLR) proposed as an indicator of systemic inflammatory response may predict clinical outcome in some cancer, such as head and neck tumor, gastric cancer,etc. However, the value of ratio is varied in different cancers. The aim of this study is to further clarify the prognostic significance of the NLR before chemoradiation in locally advanced rectal cancer and its relation with radiation response.Methods:Between January 2006 and December 2011,199 consecutive locally advanced rectal cancer patients undergoing neoadjuvant chemoradiation in Shanghai Cancer Center were enrolled and analyzed retrospectively. Tumor responses were evaluated by pathologic finding. Baseline total white blood cell count, neutrophil, lymphocyte and platelet counts from peripheral blood were recorded. Neutrophil-lymphocyte ratio (NLR) and its relationship with clinical outcome including radiation response, OS and DFS were analyzed.Results:With ROC analysis, baseline NLR value was able to discriminate prognosis of OS well in rectal cancer patients. Multivariate analysis identified that the cut-off value of NLR>2.8 could be as an independent factor to indicate worse OS (HR, 2.101; 95%CI,1.133-3.898; P=0.019). NLR≥2.8 also showed to be associated with worse DFS in univariate analysis (HR,1.662; 95%CI,1.037-2.664; P=0.035) though with no significance in multivariate analysis (HR,1.364; 95%CI,0.840-2.215; P=0.210). There was no significant correlation of mean value of NLR to the response of chemoradiation. The mean NLR in good-response group was 2.68±1.38 and 2.77±1.38 in poor-response group with no statistical significance (P=0.703).Conclusion:An elevated baseline NLR is a valuable and easily available prognostic factor for OS in addition to tumor response after neoadjuvant therapy. Baseline NLR could be as a good candidate factor to stratify patients for treatment decision making in locally advanced rectal cancer.Part2:Predicting Significance of Mesorectal Extension Depth in T3 Rectal Cancer before Neoadjuvant ChemoradiationObjective:Although neoadjuvant chemoradiation has been taken as a standard care for locally advanced rectal cancer, the treatment strategies for T3 stage rectal cancer still remain controversial since its different tumor extension depth. The aim of this study is to investigate the association of mesorectal extension depth before neoadjuvant chemoradiation with pathological outcome and to provide evidence for individualized treatment in T3 rectal cancer.Methods:Retrospective analysis was performed on the clinical records of 73 consecutive rectal cancer patients treated with neoadjuvant chemoradiation and radical surgury in Shanghai Cancer Center from January 2010 to December 2012. All patients underwent high-resolution MRI and the depth of mesorectal extension, lymph node status, tumor length and mesorectal fascia status were evaluated. The category T3 was subdivided according to the measurement of the maximal tumor invasion beyond the outer border of the muscularis propria:T3a (<5mm), T3b (5-10mm) and T3c (>10mm). The association of mesorectal extension depth, other MRI and clinical features with short-term effect was analyzed, especially with pathological complete response(pCR).Results:T3a, T3b and T3c accounted for 19.2%,64.4% and 16.4% in 73 rectal cancer patients who underwent high resolution MRI, respectively.42.9% of T3a patients achieved pathological complete response, significantly higher than in T3b (14.9%) and T3c (0) (P=0.017).45.5% of patients with negative lymph nodes achieved pathological complete response (pCR), significantly higher than in patients with positive lymph nodes (12.9%) (P=0.021).Conclusions:T3a rectal cancer patients are more likely to achieve pCR than T3b and T3c after neoadjuvant chemoradiation. The maximal tumor invasion beyond the outer border of the muscularis propria less than 5mm may act as a predictive factor and guide the follow-up treatment of T3 rectal cancer.Part3:Long-term Prognostic Significance of Morphologic Alteration of Locally Advanced Rectal Cancer to Neoadjuvant ChemoradiationObjective:There is a series of morphologic alteration of rectal cancer after neoadjuvant chemoradiation, including tumor regression, producing mucin pools, fibrosis and inflammation, etc. However, the relationship between these patterns of morphologic alteration and prognosis remains controversial except ypTNM staging. The aim of this study is to clarify the prognostic significance of these alterations.Methods:Between January 2006 and March 2013,325 locally advanced rectal cancer patients treated with neoadjuvant chemoradiation in Shanghai Cancer Center were enrolled and analyzed retrospectively. Pathologic evaluation was performed by one specialized pathologist unaware of the clinical findings. The prognostic significance of TRG score, mucin pools, inflammation as well as conventional pathologic staging were assessed.Results:Up to 19.1% patients achieved pCR after chemoradiation. The 5-year DFS was 53.2% and OS was 61.9% for all patients. Accumulative 5-year recurrence rate was 13%. Five-year DFS for TRG0-1 group is 64.4%,38.4% for TRG2-3 group (P=0.021) and OS is 75.8% vs.46.9%(P=0.021), respectively.In patients with the same ypT stage, TRG score was not associated with survival. Patients with mucin pools had a shorter DFS (41.6% vs.59.4%, P=0.025) but OS did not differ between two groups (63.1% vs.64.2%, P=0.11). In the pCR group, neither DFS nor OS is related to acellular mucin pools. The DFS in patients with fibrotic type and fibroinflammatory type was not significantly different (50.3% vs.56.7%, P=0.067) as well as for OS (63.4% vs.57.9%, P=0.468). In multivariate analysis, palliative surgery and ypⅡ-Ⅲ were significantly associated with worse DFS. For OS, mucin-producing carcinoma, palliative surgery and ypⅡ-Ⅲ were independent prognostic factors.Conclusion:The ypTNM stage was the most significant prognostic factor for rectal cancer undergoing neoadjuvant chemoradiation. Palliative surgery and mucin-producing carcinoma were also associated with worse survival. TRG score was not an independent prognostic factor. Mucin pools did not influence OS but might suggest a more aggressive tumor biology. Local inflammation response was not associated with survival. |
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